PRESENCE AND BIOLOGICAL ACTIVITY OF C-TYPE NATRIURETIC PEPTIDE-DEPENDENT GUANYLATE CYCLASE-COUPLED RECEPTOR IN THE PENILE CORPUS CAVERNOSUM

Abstract

Purpose: To investigate the presence of C-type natriuretic peptide 1-22 (CNP)-dependent guanylyl cyclase (GC)-coupled receptor and its biological function in the penile erectile smooth muscle. Materials and Methods: Experiments have been done in rabbit and rat to detect cyclic GMP (cGMP) generation by the activation of particulate GC by natriuretic peptides (NPs) in cavernosal membrane, to localize precise receptor using a quantitative in vitro autoradiography of the snap frozen sections, to define natriuretic peptide receptor (NPR) mRNA using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique and to monitor changes of erectile smooth muscle tone by NPs in the penile tissue strips. Results: Productions of cGMP by particulate GC in the corpus cavernosum membranes of rabbit and rat were stimulated by CNP, atrial natriuretic peptide 1-28 (ANP) and brain natriuretic peptide 1-26 (BNP) with a rank order of potency of CNP > BNP > ANP. HS-142-1, a selective antagonist for the GC-coupled NPR, inhibited the CNP-stimulated cGMP production in corpus cavernosal membrane of rabbit and rat. Specific¹²⁵ I-[Tyr⁰]-CNP bindings were localized in the corpus cavernosal smooth muscle of rabbit with K_d of 19.92 +/− 3.38 nM. and B_max of 734.64 +/− 139.63 amol./mm². B-subtype of NPR mRNA was detected in the penile corpus cavernosum of rat using RT-PCR technique. CNP relaxed the smooth muscle contracted by N omega-nitro-L-arginine methylester (L-NAME). Conclusions: These results suggest for the first time that CNP modulates the erectile smooth muscle tone of penis by predominant activation of B-subtype of NPR augmentation of cGMP production via particulate GC.